| Project/Area Number |
18K15955
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Kagoshima University |
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Principal Investigator |
TAKAGI KOICHI 鹿児島大学, 医歯学総合研究科, 特任助教 (40707866)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 肺線維症 / TET遺伝子 / DNAメチル化 / TET / DNAメチル化アレイ / microRNA-22 / IPF / TGFβR |
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| Outline of Final Research Achievements |
The purpose of the present study was to clarify the association between miRNA22 and TET gene in idiopathic pulmonary fibrosis. A model of lung fibrosis was created in miRNA22KO mice and compared with wild type mice, but no significant difference was observed in lung fibrosis. Therefore, we focused our research on the TET gene and proceeded with the research. The expression of TET1 gene was attenuated in the lung of a model mouse of pulmonary fibrosis. The expression of αSMA was enhanced in the cultured human lung fibroblasts in which the expression of TET1 gene was attenuated. Inhibition of lung fibrosis was observed by intratracheal administration of a DNA methylation inhibitor to pulmonary fibrosis model mice. The present study suggested that the TET gene is involved in the pathological condition of pulmonary fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究成果より、肺線維症では肺組織内でTET１遺伝子の発現抑制が誘導されることでDNAメチル化が促進し、肺内の線維芽細胞が筋線維芽細胞に分化することで肺の線維化が亢進することが示唆された。ブレオマイシン誘導肺線維症モデルマウスにおいて、DNAメチル化阻害薬により肺線維化が抑制されたことより、難治性肺疾患である肺線維症において、肺局所のDNAメチル化を抑制することが新規治療となりうる可能性がある。
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